SERS nanostructures with engineered active peptides against an immune checkpoint protein.

The immune checkpoint programmed death ligand 1 (PD-L1) protein is expressed by tumor cells and it suppresses the killer activity of CD8+ T-lymphocyte cells binding to the programmed death 1 (PD-1) protein of these immune cells. Binding to either PD-L1 or PD1 is used for avoiding the inactivation of CD8+ T-lymphocyte cells. We report, for the first time, Au plasmonic nanostructures with surface-enhanced Raman scattering (SERS) properties (SERS nanostructures) and functionalized with an engineered peptide (CLP002: Trp-His-Arg-Ser-Tyr-Tyr-Thr-Trp-Asn-Leu-Asn-Thr), which targets PD-L1. Molecular dynamics calculations are used to describe the interaction of the targeting peptide with PD-L1 in the region where the interaction with PD-1 occurs, showing also the poor targeting activity of a peptide with the same amino acids, but a scrambled sequence. The results are confirmed experimentally since a very good targeting activity is observed against the MDA-MB-231 breast adenocarcinoma cancer cell line, which overexpresses PD-L1. A good activity is observed, in particular, for SERS nanostructures where the CLP002-engineered peptide is linked to the nanostructure surface with a short charged amino acid sequence and a long PEG chain. The results show that the functionalized SERS nanostructures show very good targeting of the immune checkpoint PD-L1.

Investigation into the Influence of the Process Parameters on the Stability of a Poly(Vinyl)-Alcohol-Based Coating System.

Most tablets put on the market are coated with polymers soluble in water. The Opadry II 85 series from Colorcon Inc., is a family of PVA-based products marketed since the 1990s. Despite numerous publications on the properties of PVA, to date, limited work has been undertaken to determine the physico-chemical parameters (i.e., UV light, high temperature, and relative humidity) that could affect the performance of PVA-based coatings. To this end, we performed artificial ageing processes on samples made of Opadry Orange II or of some selected components of this coating and analysed them by means of a multidisciplinary approach, using, for example, FTIR, NMR, rheology, and DMTA measurements. In this way, we analysed the influence of the critical components of the Opadry Orange II formula, such as titanium dioxide and aluminium hydroxide, on the coating characteristics under ageing conditions.

Consensus Paper: Current Perspectives on Abstract Concepts and Future Research Directions.

concepts are relevant to a wide range of disciplines, including cognitive science, linguistics, psychology, cognitive, social, and affective neuroscience, and philosophy. This consensus paper synthesizes the work and views of researchers in the field, discussing current perspectives on theoretical and methodological issues, and recommendations for future research. In this paper, we urge researchers to go beyond the traditional abstract-concrete dichotomy and consider the multiple dimensions that characterize concepts (e.g., sensorimotor experience, social interaction, conceptual metaphor), as well as the mediating influence of linguistic and cultural context on conceptual representations. We also promote the use of interactive methods to investigate both the comprehension and production of abstract concepts, while also focusing on individual differences in conceptual representations. Overall, we argue that abstract concepts should be studied in a more nuanced way that takes into account their complexity and diversity, which should permit us a fuller, more holistic understanding of abstract cognition.

Ultrasound-Stimulated PVA Microbubbles as a Green and Handy Tool for the Cleaning of Cellulose-Based Materials.

One of the main issues in the cultural heritage field of restoration chemistry is the identification of greener and more effective methods for the wet cleaning of paper artefacts, which serve as witnesses to human history and custodians of cultural values. In this context, we propose a biocompatible method to perform wet cleaning on paper based on the use of 1 MHz ultrasound in combination with water-dispersed polyvinyl alcohol microbubbles (PVAMBs), followed by dabbing with PVA-based hydrogel. This method can be applied to both old and new papers. FTIR spectroscopy, X-ray diffraction, HPLC analysis, pH measurements and tensile tests were performed on paper samples, to assess the efficacy of the cleaning system. According to the results, ultrasound-activated PVAMB application allows for an efficient interaction with rough and porous cellulose paper profiles, promoting the removal of cellulose degradation byproducts, while the following hydrogel dabbing treatment guarantees the removal of cleaning materials residues. Moreover, the results also pointed out that after the treatment no thermal or mechanical damages had affected the paper. In conclusion, the readability of these kinds of artifacts can be improved without causing an alteration of their structural properties, while mitigating the risk of ink diffusion.

Grounded Cognition, Linguistic Relativity, and Abstract Concepts.

Kemmerer's paper convincingly claims that the grounded cognition model (GCM) entails linguistic relativity. Here, we underline that tackling linguistic relativity and cultural differences is vital for GCM. First, it allows GCM to focus more on flexible rather than stable aspects of cognition. Second, it highlights the centrality of linguistic experience for human cognition. While GCM-inspired research underscored the similarity between linguistic and nonlinguistic concepts, it is now paramount to understand when and how language(s) influence knowledge. To this aim, we argue that linguistic variation might be particularly relevant for more abstract concepts-which are more debatable and open to revisions.

Molecular origin of the two-step mechanism of gellan aggregation.

Among hydrocolloids, gellan is one of the most studied polysaccharides due to its ability to form mechanically stable gels. Despite its long-standing use, the gellan aggregation mechanism is still not understood because of the lack of atomistic information. Here, we fill this gap by developing a new gellan force field. Our simulations offer the first microscopic overview of gellan aggregation, detecting the coil to single-helix transition at dilute conditions and the formation of higher-order aggregates at high concentration through a two-step process: first, the formation of double helices and then their assembly into superstructures. For both steps, we also assess the role of monovalent and divalent cations, complementing simulations with rheology and atomic force microscopy experiments and highlighting the leading role of divalent cations. These results pave the way for future use of gellan-based systems in a variety of applications, from food science to art restoration.

An Insight into the Degradation Processes of the Anti-Hypertensive Drug Furosemide.

Furosemide (FUR), an active pharmaceutical ingredient (API) belonging to a group of drugs known as loop diuretics, has widespread use, but, is characterized by a strong instability to light, which causes chemical transformations that could give a yellowing phenomenon and have a significant impact from a health and marketing point of view. Many studies have tried to explain this phenomenon under different experimental conditions, but no detailed explanation of the yellowing phenomenon has been provided. This work, unlike the others, provides an overall view and explanation of the behavior of FUR in relation to the yellowing phenomenon, both in the solution and in solid state, considering several aspects, such as light exposure, presence of oxygen, and moisture effects.

Abstractness emerges progressively over the second year of life.

words, terms not referring to here and now, are acquired slowly in infancy. They are difficult to acquire as they are more detached from sensory modalities than concrete words. Recent theories propose that, because of their complexity, other people are pivotal for abstract concepts' acquisition and use. Eight children (4 girls) and their mothers were observed longitudinally and extensively from 12 to 24 months of age. Video recordings of mother-infant free play with toys were done every two weeks in a laboratory setting with families in the USA. Children progressively use a range of words referring to abstract concepts, with a major shift from 12 to 15 months and again from 22 to 24 months, but the qualitative data testify an incremental growth of abstract concepts. We identified a progression in the acquisition of words denoting abstract concepts in relation to the overall productive vocabulary, suggesting that having more abstract terms in one's vocabulary promotes faster language acquisition.

Bodily, emotional, and public sphere at the time of COVID-19. An investigation on concrete and abstract concepts.

The outbreak of Covid-19 pandemics has dramatically affected people's lives. Among newly established practices, it has likely enriched our conceptual representations with new components. We tested this by asking Italian participants during the first lockdown to rate a set of diverse words on several crucial dimensions. We found concepts are organized along a main axis opposing internal and external grounding, with fine-grained distinctions within the two categories underlining the role of emotions. We also show through a comparison with existing data that Covid-19 impacted the organization of conceptual representations. For instance, subclasses of abstract concepts that are usually distinct converge into a unitary group, characterized by emotions and internal grounding. Additionally, we found institutional and Covid-19 related concepts, for which participants felt more the need for others to understand the meaning, clustered together. Our results show that the spread of Covid-19 has simultaneously changed our lives and shaped our conceptual representations.

Inspection on the Mechanism of SARS-CoV-2 Inhibition by Penciclovir: A Molecular Dynamic Study.

In recent years, humanity has had to face a critical pandemic due to SARS-CoV-2. In the rapid search for effective drugs against this RNA-positive virus, the repurposing of already existing nucleotide/nucleoside analogs able to stop RNA replication by inhibiting the RNA-dependent RNA polymerase enzyme has been evaluated. In this process, a valid contribution has been the use of in silico experiments, which allow for a rapid evaluation of the possible effectiveness of the proposed drugs. Here we propose a molecular dynamic study to provide insight into the inhibition mechanism of Penciclovir, a nucleotide analog on the RNA-dependent RNA polymerase enzyme. Besides the presented results, in this article, for the first time, molecular dynamic simulations have been performed considering not only the RNA-dependent RNA polymerase protein, but also its cofactors (fundamental for RNA replication) and double-strand RNA.

Extra-Low Dosage Graphene Oxide Cementitious Nanocomposites: A Nano- to Macroscale Approach.

The impact of extra-low dosage (0.01% by weight of cement) Graphene Oxide (GO) on the properties of fresh and hardened nanocomposites was assessed. The use of a minimum amount of 2-D nanofiller would minimize costs and sustainability issues, therefore encouraging the market uptake of nanoengineered cement-based materials. GO was characterized by X-ray Photoelectron Spectroscopy (XPS), Fourier-transform infrared spectroscopy (FTIR), Atomic Force Microscopy (AFM), X-ray Diffraction (XRD), and Raman spectroscopy. GO consisted of stacked sheets up to 600 nm × 800 nm wide and 2 nm thick, oxygen content 31 at%. The impact of GO on the fresh admixtures was evaluated by rheology, flowability, and workability measurements. GO-modified samples were characterized by density measurements, Scanning Electron Microscopy (SEM) analysis, and compression and bending tests. Permeability was investigated using the boiling-water saturation technique, salt ponding test, and Initial Surface Absorption Test (ISAT). At 28 days, GO-nanocomposite exhibited increased density (+14%), improved compressive and flexural strength (+29% and +13%, respectively), and decreased permeability compared to the control sample. The strengthening effect dominated over the adverse effects associated with the worsening of the fresh properties; reduced permeability was mainly attributed to the refining of the pore network induced by the presence of GO.

From Affordances to Abstract Words: The Flexibility of Sensorimotor Grounding.

The sensorimotor system plays a critical role in several cognitive processes. Here, we review recent studies documenting this interplay at different levels. First, we concentrate on studies that have shown how the sensorimotor system is flexibly involved in interactions with objects. We report evidence demonstrating how social context and situations influence affordance activation, and then focus on tactile and kinesthetic components in body-object interactions. Then, we turn to word use, and review studies that have shown that not only concrete words, but also abstract words are grounded in the sensorimotor system. We report evidence that abstract concepts activate the mouth effector more than concrete concepts, and discuss this effect in light of studies on adults, children, and infants. Finally, we pinpoint possible sensorimotor mechanisms at play in the acquisition and use of abstract concepts. Overall, we show that the involvement of the sensorimotor system is flexibly modulated by context, and that its role can be integrated and flanked by that of other systems such as the linguistic system. We suggest that to unravel the role of the sensorimotor system in cognition, future research should fully explore the complexity of this intricate, and sometimes slippery, relation.

Differences and similarities in the conceptualization of COVID-19 and other diseases in the first Italian lockdown.

Several studies have highlighted the flexible character of our conceptual system. However, less is known about the construction of meaning and the impact of novel concepts on the structuring of our conceptual space. We addressed these questions by collecting free listing data from Italian participants on a newly-and yet nowadays critical-introduced concept, i.e., COVID-19, during the first Italian lockdown. We also collected data for other five illness-related concepts. Our results show that COVID-19's representation is mostly couched in the emotional sphere, predominantly evoking fear-linked to both possible health-related concerns and social-emotional ones. In contrast with initial public debates we found that participants did not assimilate COVID-19 neither completely to severe illnesses (e.g., tumor) nor completely to mild illnesses (e.g., flu). Moreover, we also found that COVID-19 has shaped conceptual relations of other concepts in the illness domain, making certain features and associations more salient (e.g., flu-fear; disease-mask). Overall, our results show for the first time how a novel, real concept molds existing conceptual relations, testifying the malleability of our conceptual system.

Toward a Reversible Consolidation of Paper Materials Using Cellulose Nanocrystals.

An innovative consolidation strategy for degraded paper is presented based on the reversible application of cellulose nanocrystals as sustainable fillers to reinforce mechanical properties and resistance to further degradation. The compatibility and efficacy of the proposed consolidation treatment are assessed first on pure cellulose paper, used as a model, by reliable techniques such as field emission scanning electron microscopy, atomic force microscopy, tensile tests, X-ray powder diffraction, and Fourier transform infrared spectroscopy, evidencing the influence of the surface functionalization of nanocellulose on the consolidation and protection effects. Then, the consolidation technique is applied to real aged paper samples from Breviarium romanum ad usum Fratrum Minorum S.P. (1738), demonstrating the promising potential of the suggested approach. Amperometric measurements, carried out with a smart electrochemical tool developed in our laboratory, demonstrate the reversibility of the proposed treatment by removal of the nanocrystalline cellulose from the paper surface with a suitable cleaning hydrogel. This completely new feature of the consolidation treatment proposed here satisfies a pivotal requisite in cultural heritage conservation because the methodological requirement for the ″reversibility″ of any conservation measure is a fundamental goal for restorers. A paper artifact, in fact, is subject to a number of natural and man-made hazards, inducing continuous degradation. With time, monitoring and consolidation actions need to be often performed to ensure conservation, and this tends to modify the status quo and compromise the artifact integrity. Removable treatments can potentially avoid erosion of the artifact integrity.

Ultrasound-Stimulated PVA Microbubbles for Adhesive Removal from Cellulose-Based Materials: A Groundbreaking Low-Impact Methodology.

In this work, we shed new light on ultrasound contrast agents applied to the field of cultural heritage as an invaluable fine-tune cleaning tool for paper artworks. In this context, one of the primary and challenging issues is the removal of modern adhesives from paper artifacts. Modern adhesives are synthetic polymers whose presence enhances paper degradation and worsens its optical features. A thorough analytical and high-spatial-resolution combined study was successfully performed to test the capability of poly(vinyl alcohol)-based microbubbles stimulated by a proper noninvasive 1 MHz ultrasound field exposure in removing these adhesives from paper surfaces, in the absence of volatile invasive and toxic chemicals and without damaging paper and/or leaving residues. We demonstrate that poly(vinyl alcohol)-shelled microbubbles are suitable for interacting with paper surfaces, targeting and boosting in a few minutes the nondamaging removal of adhesive particles from paper samples thanks to their peculiar shell composition together with their ultrasound dynamics.

Assessing the impact of previous experience on lie effects through a transfer paradigm.

Influential lines of research propose dual processes-based explanations to account for both the cognitive cost implied in lying and for that entailed in the resolution of the conflict posited by Simon tasks. The emergence and consistency of the Simon effect has been proved to be modulated by both practice effects and transfer effects. Although several studies provided evidence that the lying cognitive demand may vary as a function of practice, whether and how transfer effects could also play a role remains an open question. We addressed this question with one experiment in which participants completed a Differentiation of Deception Paradigm twice (baseline and test sessions). Crucially, between the baseline and the test sessions, participants performed a training session consisting in a spatial compatibility task with incompatible (condition 1) or compatible (condition 2) mapping, a non-spatial task (condition 3) and a no task one (condition 4). Results speak in favour of a modulation of individual performances by means of an immediate prior experience, and specifically with an incompatible spatial training.

From nanoaggregates to mesoscale ribbons: the multistep self-organization of amphiphilic peptides.

This paper reports atomic force microscopy results and molecular dynamics simulations of the striking differences of long-term self-organization structures of negatively charged (AcA4)2KD (double tail) and AcA4D (single tail) peptides, respectively, forming micrometer-long, linearly ordered ribbon-like structures and nanometer-sized, unstructured, round-shaped aggregates. The subsequent formation steps of the long-range nanoribbons, experimentally observed only for the "double tail" (AcA4)2KD peptide, are analyzed in detail, showing that the initial "primary" unstructured round-shaped aggregates progressively evolve into longer nanofilaments and into micrometer-long, network-forming nanoribbon moieties. In particular, the long-range self-organization of the "double tail" peptides appears to be closely related to electrostatically driven diffusional motions of the primary aggregates and nanofilaments. The diffusional freedom degrees are prompted by the formation of a dynamic ternary air/liquid/substrate interface, due to the water evaporation process from the ultrathin films of the peptide solution cast onto a solid mica substrate. Overall, the initial aggregation of unstructured round-shaped moieties, for both the peptides, can be seen as an entropy-driven process, involving the intra- and intermolecular interactions of hydrophobic parts of the peptides, while the further formation of long nanoribbons, only for "double tail" peptides, can be viewed in terms of an enthalpy-driven process, mainly due to the predominant electrostatic interactions between the charged heads of the interacting peptides. The role of the solid-liquid interface, as the locus of the enthalpy-driven linear organization, is also highlighted.

Phytocomplex Influences Antimicrobial and Health Properties of Concentrated Glycerine Macerates.

The purpose of this study was to correlate the chemical composition of four commercial concentrated glycerine macerates (C-GMs), produced through the same extraction method, with their in vitro antimicrobial, antioxidant, and immunomodulatory properties, in order to evaluate their potential for healing upper airway diseases. C-GMs of Carpinus betulus (CB), Ficus carica (FC), Alnus glutinosa (AG) and Ribes nigrum (RN) were studied. The quality was evaluated using HPLC and IM-SPME/GC-MS systems; anti-oxidant and anti-microbial activities were assessed by the respective DPPH test, and micro-broth dilution test performed against 10 strains of Streptococcus pyogenes and 10 probiotic strains. ELISA and MTT tests were used to assess the immunomodulatory activity and the cytotoxicity of C-GMs, respectively. A significant correlation was found between the number of active compounds and the in vitro C-GMs effectiveness. Furthermore, the C-GMs of AG showed the best anti-microbial activity on pathological strains and, together with CB, the best anti-oxidant activity. The ELISA test exhibited a good immunomodulatory activity of RN. In vitro data support the integrated use of C-GMs of CB, AG, and RN in presence of airway diseases, and highlight the importance of standard procedures in cultivation, harvest and post-harvest treatments, as a premise for C-GMs with consistent characteristics.

Conceptualisations of landscape differ across European languages.

Policies aimed at sustainable landscape management recognise the importance of multiple cultural viewpoints, but the notion of landscape itself is implicitly assumed to be homogeneous across speech communities. We tested this assumption by collecting data about the concept of "landscape" from speakers of seven languages of European origin. Speakers were asked to freely list exemplars to "landscape" (a concrete concept for which the underlying conceptual structure is unclear), "animals" (a concrete and discrete concept) and "body parts" (a concrete concept characterised by segmentation). We found, across languages, participants considered listing landscape terms the hardest task, listed fewest exemplars, had the least number of shared exemplars, and had fewer common co-occurrence pairs (i.e., pairs of exemplars listed adjacently). We also found important differences between languages in the types of exemplars that were cognitively salient and, most importantly, in how the exemplars are connected to each other in semantic networks. Overall, this shows that "landscape" is more weakly structured than other domains, with high variability both within and between languages. This diversity suggests that for sustainable landscape policies to be effective, they need to be better tailored to local conceptualisations.